School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
Mol Biol Evol. 2022 Jun 2;39(6). doi: 10.1093/molbev/msac118.
Whole-genome duplications (WGDs) have occurred in many eukaryotic lineages. However, the underlying evolutionary forces and molecular mechanisms responsible for the long-term retention of gene duplicates created by WGDs are not well understood. We employ a population-genomic approach to understand the selective forces acting on paralogs and investigate ongoing duplicate-gene loss in multiple species of Paramecium that share an ancient WGD. We show that mutations that abolish protein function are more likely to be segregating in retained WGD paralogs than in single-copy genes, most likely because of ongoing nonfunctionalization post-WGD. This relaxation of purifying selection occurs in only one WGD paralog, accompanied by the gradual fixation of nonsynonymous mutations and reduction in levels of expression, and occurs over a long period of evolutionary time, "marking" one locus for future loss. Concordantly, the fitness effects of new nonsynonymous mutations and frameshift-causing indels are significantly more deleterious in the highly expressed copy compared with their paralogs with lower expression. Our results provide a novel mechanistic model of gene duplicate loss following WGDs, wherein selection acts on the sum of functional activity of both duplicate genes, allowing the two to wander in expression and functional space, until one duplicate locus eventually degenerates enough in functional efficiency or expression that its contribution to total activity is too insignificant to be retained by purifying selection. Retention of duplicates by such mechanisms predicts long times to duplicate-gene loss, which should not be falsely attributed to retention due to gain/change in function.
全基因组复制 (WGD) 在许多真核生物谱系中发生过。然而，导致 WGD 产生的基因副本长期保留的潜在进化力量和分子机制还没有被很好地理解。我们采用群体基因组学的方法来了解作用于同源基因的选择压力，并研究了 Paramecium 多个物种中正在发生的重复基因丢失，这些物种共享一个古老的 WGD。我们表明，使蛋白质功能丧失的突变更有可能在保留的 WGD 同源基因中分离，而不是在单拷贝基因中，这很可能是由于 WGD 后持续的非功能化。这种净化选择的放松仅发生在一个 WGD 同源基因中，伴随着非同义突变的逐渐固定和表达水平的降低，而且发生在很长的进化时间内，“标记”一个未来丢失的基因座。一致地，新的非同义突变和移码缺失引起的框移突变的适应度效应在高度表达的拷贝中比其表达较低的同源基因更具破坏性。我们的结果提供了 WGD 后基因副本丢失的新的机制模型，其中选择作用于两个副本基因的功能活性总和，允许两个基因在表达和功能空间中漫游，直到一个副本基因最终在功能效率或表达上退化到足够多，以至于其对总活性的贡献太小而无法被净化选择保留。通过这种机制保留副本可以预测重复基因丢失的时间很长，不应该由于功能获得/改变而错误地归因于保留。
